Abstract
Human old aged unmutated chronic lymphocytic leukemia U-CLL are the TCL1(+)ZAP70(+)CD5(+) B cells. Since CD5 makes the BCR signaling tolerance, ZAP70 increased in U-CLL not only TCL1(+) alone. In mice, TCL1 (TCL1A) is the negative from neonate to old aged, as TC(-). V(H)8-12/V(k)21-5 is the anti-thymocyte/Thy-1 autoreactive ATA B cell. When ATA μκTg generation in mice, ATA B cells are the neonate generated CD5(+) B cells in B-1, and in the middle age, CD5(+) can be down or continuously CD5(+), then, old aged CLL/lymphoma generation with increased CD11b in TC(-)ZAP70(-)CD5(-) or TC(-)ZAP70(+)CD5(+). In this old aged TC(-)ATA B microarray analysis showed most similar to human CLL and U-CLL, and TC(-)ZAP70(+)CD5(+) showed certain higher present as U-CLL. Original neonate ATA B cells showed with several genes down or further increase in old aged tumor, and old aged T-bet(+)CD11c(+), CTNNB1(hi), HMGB(hi), CXCR4(hi), DPP4(hi) and decreased miR181b. These old aged increased genes and down miR181b are similar to human CLL. Also, in old age ATA B cell tumor, high CD38(++)CD44(++), increased Ki67(+) AID(+), and decreased CD180(-) miR15O(low) are similar to U-CLL. In this old aged ATA B, increased TLR7,9 and Wnt10b. TC(+)Tg generated with ATAμκTg mice occurred middle age tumor as TC(+)ZAP70(-)CD5(+) or TC(+)ZAP70(+)CD5(+), with high NF-kB1, TLR4,6 and Wnt5b,6 without increased CD11b. Since neonatal state to age with TC(+)Tg continuously, middle age CLL/lymphoma generation is not similar to old aged generated, however, some increased in TC(+)ZAP70(+) are similar to the old age TC(-) ATA B tumor. Then, TC(-) ATA B old age tumor showed some difference to human CLL. ATA B cells showed CD11b(+)CD22(++), CD24 down, and hepcidin Hamp2(++) with iron down. This mouse V8-12 similar to human V2-5, and V2-5 showed several cancers with macrophages/neutrophils generated hepcidin(+) iron(low) or some showed hepcidin(-) iron(+) with tumor, and mouse V8-12 with different V(k)19-17 generate MZ B cells strongly increased macrophage(++) in old aged and generated intestine/colon tumor. Conclusion, neonate generated TC(-)ATA B1 cells in old aged tumor generation are CD11b(+) in the leukemia CLL together with lymphoma cancer with hepcidin-related Hamp2(++) in B-1 cell generation to control iron.